For centuries man has attempted to accelerate the healing process of pathological processes and conditions and reduce the symptoms associated with disease by the targeted administration of pharmaceutically active substances. Besides the selection of and search for suitable active substances, one problem resides in making the active substance available at the desired site of treatment. In order to minimise the side effects associated with administration, the release of the active substance should, if possible, be limited exclusively to the site of treatment. Furthermore, it is necessary in most cases, in order to optimise the effect, to maintain a posology as accurately as possible, i.e., to keep the concentration of active substance within specific range limits at the site of treatment over a predeterminable period. Conventionally active substances are applied orally, subcutaneously, intravenously or rectally. The conventional systemic administration of medicines results in considerable complications, particularly in the case of local diseases, e.g., tumours.
For many years there have therefore been increasing efforts to introduce the active substance more specifically into the body of the patient to be treated. The term ‘Local Drug Delivery’ (LDD) has been established to describe an exclusively local treatment from an implant, i.e., elution of an active substance essentially only into the tissue immediately surrounding the implant. The site of treatment at which the active substance is to exert its pharmacological action therefore lies immediately adjacent to the site of implantation.
An important area of application for LDD systems therefore lies in the improvement in biocompatibility of permanent implants such as stents, cardiac pacemakers or orthopaedic prostheses. In particular, complications caused by the presence of the implant or by the implantation should be reduced or avoided here.
The basic concept behind an administration of active substances that deviates from the LDD systems descried above, which is also applied in this invention, is that of providing a more distinct spatial separation between the site of implantation and the site of treatment. In other words, the active substance released on the implant should not act directly (locally) but should only exert its action in a region of tissue spatially separate from the implant after introduction into the body. The term ‘Regional Drug Delivery’—or briefly RDD—will be used in the following to describe this type of regional active substance administration.
In some symptoms, e.g., locally limited tumours, active substances can be administered via the vascular system of the tissue to be treated. For this purpose it is necessary to introduce the implant into a vessel that lies downstream from the treatment site. A state of the art approach consists, for example, in injecting into the vessel a polymeric matrix containing the active substance. The matrix is designed so that it is converted immediately after injection to a tough film which adheres to the vascular walls. This film containing the active substance gradually decomposes, releasing the active substance. However, it is very difficult in practice to achieve such a pinpoint injection into the vessel concerned, which may lead to further complications, due to formation of thrombi for example. Finally, a posology also depends on the thickness of the film, i.e., it is difficult to predict the release characteristic that actually exists.